Breast cancer is a proliferative disease of mammary epithelial cells and estrogen has been shown to stimulate cell proliferation of these cells both in culture and in mice (Soto and Sonnenschein, 1985; Osborne, 1981). Xenoestrogens have been proposed to stimulate cell proliferation through binding and activating estrogen receptors (ERs) (Miller et al., 1993; Hoffman, 1992). The incidence of breast cancer has been steadily rising during the past two or three decades, a trend characterized by increasing rates among estrogen-responsive tumors, by continuing increases among older women, and by growing numbers in both developed and developing countries (Harris et al., 1992). Between 1973–1980, the incidence of breast cancer in the United States increased a modest 8% among women under 50 years of age, while it rose 32.1% among women in the age group of 50 years or older (Reese et al., 1991). This upward shift is consistent with the historical pattern of accumulation of organochlorine insecticides residues (xenoestrogens) in the environment (Mussalo-Rauhamaa et al., 1990; Wolff et al., 1993; Davis et al., 1993). Breast cancer is also the second leading cause of cancer deaths in women and it is estimated that in 1998, there will be an additional 43,900 deaths due to breast cancer. Environmental estrogens or endocrine disruptors have been suggested to play a role in the etiology or promotion of breast cancer (Davis et al., 1993; Dewailly et al., 1994). Experimental evidence reveals that xenoestrogens affect estrogen production and metabolism and are among the risk factors that cause breast cancer (Nelson, 1978; Berthois et al., 1986; Henderson et al., 1993; Jobling et al., 1995; Dees et al., 1997). Most of the known risk factors for breast cancer, which at least account for 30% of cases (Henderson et al., 1993) are linked with total life-time exposure to reproductive chemicals such as estrogen and xenoestrogens.
It appears evident that soft tissue cancer in mammals is increasing every year as a result of increased estrogen levels and increased exposure to environmental xenoestrogens. For example, the number of prescriptions of estrogen for women in menopause is rapidly increasing, presently estimated at 50,000,000 prescriptions annually in the United States alone. This increasing use of estrogen partially accounts for the higher risk of breast cancer in both young and middle-aged women. Estrogen is present in all mammals and is essential in women for reproductive organs such as ovary, uterus, breast, etc. In men, however, estrogen is required for sperm production and maturation. The abusive use of estrogen prescribed for women is at least partially responsible for the development of soft tissue cancers, especially breast cancer. It is therefore desirable to antagonize or counteract the adverse effects of estrogen in women.
The current FDA-approved treatments, e.g., tamoxifen, in the United States are effective to some extent in some of the female population in antagonizing the adverse effects of estrogen. Unfortunately, these treatments are not totally effective and may themselves cause additional health related effects, such as uterine cancer. Thus, if one could identify compounds that would make the current treatments more effective, or would work in conjunction with, or in lieu of, the present treatments, it is possible some of these adverse side effects would be alleviated or even eliminated. A possible source of alternative treatments are natural, non-toxic compounds. It is proposed that these compounds would advantageously provide for safer and more effective treatments.
The current literature suggests the use of certain signal transduction modulators as treatments for breast and colon cancer. The use of certain monoterpenoid plant essential oils (alpha-terpineol, linalool, and limonene) is also suggested as a potential treatment for breast cancer. These monoterpenoids however are not totally effective and have been proven to be weak anti-proliferative cancer products. In addition, these data do not suggest the capability of these compounds to antagonize the action of estrogen. This may raise the question of how this product may interact in women with estrogen supplement. None of the data disclose the combination of plant essential oils with signal transduction modulators to enhance the anti-proliferative and anti-estrogenic action of the plant essential oils without additional safety concerns.
Accordingly, there is a great need for novel pharmaceuticals that may be effectively and safely used in the prevention or treatment of soft tissue cancers in mammals.